Abstract: Based on the gate-related receptor hypothesis, modelling and analysis of interactions of flecainide with cardiac sodium channels and the gate-related receptor were performed by computer simulation. Model-predicted apparent rates of onset off lecainide (1 μmol/L) blocking were 0.586, 0.128, 0.071, 0.042 and 0.030AP^-1 at stimulation frequencies of 0.1, 0.5, 1.0, 2.0 and 3.3 Hz, respectively. The estimated time constant of recovery from block by flecainide was 17.45 s. These results are in agreement with documented experimental data. The analysis of gate-related receptor showed that the binding and unbinding of flecainide is modulated by anactivation process. No shift of h∞ curve but a significant decrease of m³∞ curve was found in the presence of flecainide (1 μmol/L). These findings sugnficant that flecainide binds to the activation gate-related receptor, and may be trapped in the channel by the activation gate.

Key words: Fleainide, Sodium channel, Antiarrhythmic agents, Computer simulation, Gaterelated receptor